The goal of this project is to utilize ERP, autonomic variables, and behavioral measures of performance on mental tasks to study the role of attentional biases in responses to drug- and traumatic stress-related cues in individuals with substance use disorder (SUD) with comorbid posttraumatic stress disorder (PTSD). Dense-array ERPs, heart rate, and skin conductance responses will be assessed during exposure to a battery of cognitive tasks containing emotional, drug- and traumatic stress-relevant cues. Specific aim I am to investigate physiological patterns of emotional reactivity in a gender category judgment task by contrasting ERP and autonomic responses to images of facial expression of affect and neutral faces in four groups of subjects (SUD-PTSD, SUD-only, PTSD-only, and controls). We will use images of facial expressions of fear and happiness to elicit emotional interference during task. We predict enhanced ERP and autonomic reactivity to expression of fear in a group of dual and PTSD patients as compared to SUD and control groups. We predict that this process will be reflected in an automatic orienting to fearful face images. The aim II is to examine ERPs to drug- and trauma-associated stimuli, and investigate how heightened orienting to these motivationally salient distracters will interfere with cognitive functions during performance on a three-category oddball task with verbal and pictorial stimuli. We predict that dual patients will show enhanced reactivity to the task-irrelevant drug- and threat-related cues which negatively affects processing of task-relevant stimuli. Specific aim III is to investigate the effects of cocaine abuse on prefrontal executive top-down control and assess response inhibition in a continuous performance task (Go-NoGo) in four groups of subjects. We predict decreased response inhibition in dual and SUD groups vs. controls which will be expressed in a higher number of commissions and a lower amplitude of the anterior NoGo-N2 and NoGo- P3 ERP components. The abnormality in information processing in a SUD-PTSD comorbidity in our model is linked with attentional and emotional bias in responses to both threat and drug cues. We propose that SUD and PTSD are functionally related through information-processing biases which are a function of automatic processes due to a conditioned sensitization to both threat and drug-related stimuli. Decreased frontal topdown control further contributes to inability to override these automatic responses and addictive behaviors. [unreadable] [unreadable] [unreadable]